LIPID COMPOSITION OF BIPOLAR DISORDER BRAIN. Docosahexaenoic and arachidonic acid concentrations (as percent of total fatty acid) were reported reduced by 24% and 14%, respectively, in BD compared with control frontal cortex. We could not confirm this report. We did not find a significant concentration difference for either fatty acid between bipolar disorder and control frontal cortex, whether concentration was measured per gram wet weight or as a percent of the total fatty acid concentration. The differences from the earlier report relate to different sources of brain tissue (Reference 1). NEUROINFLAMMATION AND EXCITOTOXICITY IN BIPOLAR DISORDER. Ten bipolar disorder (BD) and 10 control postmortem prefrontal cortical samples (Brodmann area 9) were matched for postmortem interval, pH, age and RNA integrity number (marker of RNA tissue integrity), although the BD patients had been on specific medications. BD compared with control tissue showed lower protein and mRNA levels of NMDA receptor subunits, NR-1 and NR-3A, and higher levels of IL-1b, the IL-1 receptor (IL-1R), myeloid differentiation factor 88, nuclear factor (NF)-kB subunits, and of markers of activated astrocytes and microglia (GFAP, iNOS and CD11b). There was no significant difference in the TNFa or neuronal nNOS level between groups. These data directly demonstrate excitotoxicity and neuroinflammation in BD, with particular activation of the IL-1R cascade (Ref. 2) UPREGULATED ARACHIDONIC ACID CASCADE IN BIPOLAR DISORDER BRAIN Bipolar disorder is characterized by recurrent manic and depressive episodes, but its etiology, pathophysiology and treatment mechanisms are not clear. Postmortem frontal cortex from 10 bipolar disorder patients compared with cortex from 10 age-matched controls had significant increases in a number of arachidonic (AA) cascade markers: cytosolic mRNA and protein levels of cytosolic phospholipase A2 and cyclooxygenase-2, and the respective AP-2 and NF-kB factors regulating transcription of these enzymes. These changes are consistent with neuroinflammation and excitotoxicity in bipolar disorder. DISTURBED G-PROTEIN MEDIATED NEUROTRANSMISSION IN BIPOLAR DISORDER G-proteins couple certain neuroreceptors to signaling enzymes, and are regulated by G-protein receptor kinases (GRKs). We reported that antibipolar agents upregulated rat brain expression of GRK3. In contrast, in the present study we found decreased protein and mRNA levels of G-protein subunits &#946;and &#947;and of GRK3 in postmortem frontal cortex from bipolar patients, compared with control tissue. The positive effects of mood stabilizers on GRK3 thus may account in part for their therapeutic action in bipolar disorder (Ref. 3).